Muscle fatigue encompasses a class of acute effects which impair motor performance. The mechanisms that produce fatigue may involve all elements of the motor system, from a formulation of the descending drive provided by suprasegmental centers to a reduction in the activity of muscle contractile proteins. Recently our laboratory has proposed four themes that provide a basis for the systematic evaluation of the neural and neuromuscular mechanisms that can contribute to fatigue: (1) task dependency -- to identify the conditions that activate the various fatigue mechanisms; (2) force-fatigability relationship -- to explore the interactions between the mechanisms that result in a hyperbolic relationship between force and endurance time; (3) muscle wisdom -- to examine the association between a concurrent decline in muscle relaxation rate and motor neuron discharge during fatigue that results in an optimization of force; and (4) sense of effort -- to determine the role of perceived effort in the impairment of performance. This project addresses the first three of these themes, and several of our Aim 1 techniques permit a cellular neurophysiological approach to the sense of effort. Thus, this project is an essential component of a broadly based four-theme approach to understanding the neurobiology of muscle fatigue. Segmental motor mechanisms is a term used to describe the integrated (systems) operation of brainstem/spinal motor circuitry, motor units, muscle receptors and the segmental actions of muscle-, joint- and cutaneous afferents. This project links study of the fatigue of segmental motor mechanisms to the quadripartite approach described above. Aim 1 addresses task dependency and muscle wisdom; it involves quantifying the adaptation of motor neuron discharge during sustained and intermittent stimulation when the spinal cord is passive (i.e., not generating a rhythmic motor output) or active (i.e., when generating a rhythmic motor output). Aim 2 addresses task dependency and the force-fatigability relationship and examines how the CNS might exploit the catch-like property of skeletal muscle and the stimulus frequency-force relationship to reduce and delay fatigue. Both sets of experiments will be undertaken on decapitated turtles, an animal species which is particularly well suited for the study of spinal cord-muscle relationships. It is anticipated that these studies will contribute information on fundamental issues in motor control that have not yet been resolved. Furthermore, the work has profound implications for orthopedics, sports medicine, the fatigability that is evident in various effort syndromes that accompany higher brain malfunctions, motor recovery after brain damage, many neuromuscular diseases, peripheral neuromuscular damage, functional electrical stimulation, and the emerging field of motor prosthetics.